Angiotensin II increases fibronectin and collagen I through the beta-catenin-dependent signaling in mouse collecting duct cells

作者：Cuevas Catherina A; Gonzalez Alexis A; Inestrosa Nibaldo C; Vio Carlos P; Prieto Minolfa C^*

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2015, 308(4): F358-F365.

DOI：10.1152/ajprenal.00429.2014

• pyrvinium pamoate
• mouse collecting duct cell
• tissue homeostasis

The contribution of angiotensin II (ANG II) to renal and tubular fibrosis has been widely reported. Recent studies have shown that collecting duct cells can undergo mesenchymal transition suggesting that collecting duct cells are involved in interstitial fibrosis. The Wnt/beta-catenin signaling pathway plays an essential role in development, organogenesis, and tissue homeostasis; however, the dysregulation of this pathway has been linked to fibrosis. In this study, we investigated whether AT(1) receptor activation induces the expression of fibronectin and collagen I via the beta-catenin pathway in mouse collecting duct cell line M-1. ANG II (10(-7) M) treatment in M-1 cells increased mRNA, protein levels of fibronectin and collagen I, the beta-catenin target genes (cyclin D1 and c-myc), and the myofibroblast phenotype. These effects were prevented by candesartan, an AT(1) receptor blocker. Inhibition of the beta-catenin degradation with pyrvinium pamoate (pyr; 10(-9) M) prevented the ANG II-induced expression of fibronectin, collagen I, and beta-catenin target genes. ANG II treatment promoted the accumulation of beta-catenin protein in a time-dependent manner. Because phosphorylation of glycogen synthase kinase-3 beta (GSK-3 beta) inhibits beta-catenin degradation, we further evaluated the effects of ANG II and ANG II plus pyr on p-ser9-GSK-3 beta levels. ANG II-dependent upregulation of beta-catenin protein levels was correlated with GSK-3 beta phosphorylation. These effects were prevented by pyr. Our data indicate that in M-1 collecting duct cells, the beta-catenin pathway mediates the stimulation of fibronectin and collagen I in response to AT(1) receptor activation.

• 出版日期2015-2-15